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CARDIOVASCULAR ANESTHESIA

The Effect of Clomethiazole on Plasma Concentrations of Interleukin-6, -8, -1ß, Tumor Necrosis Factor-, and Neutrophil Adhesion Molecule Expression During Experimental Extracorporeal Circulation

D. Harmon, MMedsci FCARCSI^*, E. Coleman, Dip Lab Med, FCCP, C. Marshall, BSc ACP, W. Lan, MB^*, and G. Shorten, MD PhD^*

*Department of Anaesthesia & Intensive Care Medicine, Cork University Hospital, University College Cork; and Department of Clinical Perfusion, Cork University Hospital, Cork, Ireland

Address correspondence and reprint requests to George Shorten, MD, PhD, Department of Anesthesia & Intensive Care Medicine, Cork University Hospital, Wilton Rd., Cork, Ireland. Address e-mail to shorteng{at}shb.ie

Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1ß, tumor necrosis factor-, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37°C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 µmol/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor- were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass.

IMPLICATIONS: Enhancement of -aminobutyric acid_A-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

This article has been cited by other articles:

				W. T. McBride, N. Khalil, P. Elliott, and M. Armstrong Clomethiazole Alters Immune Function Within an Isolated Cardiopulmonary Bypass Circuit Anesth. Analg., April 1, 2004; 98(4): 1191 - 1191. [Full Text] [PDF]

Anesthesia & Analgesia® is published for the International Anesthesia Research Society® by Lippincott Williams & Wilkins with the assistance of Stanford University Libraries' HighWire Press®. Copyright 2006 by the International Anesthesia Research Society. Online ISSN: 1526-7598   Print ISSN: 0003-2999